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Vast disparities between and within American states’ responses to the COVID-19 pandemic have evoked renewed attention to whether greater centralization might enhance investments in subnational capacity and remedy subnational inequalities or instead erode subnational organizational capacity. Developments in American public education (1997–2015) offer perspective on this puzzle, which we examine by applying interrupted time series analysis to a novel dataset to assess the implications of centralization on subnational investments in administrative and technical capacity, two dimensions of organizational capacity. We find simultaneous subnational erosion in administrative capacity and growth in technical capacity following centralization, both of which appear concentrated in low-poverty areas despite centralization’s explicit antipoverty purposes. Public education reforms highlight both the challenge of dismantling subnational inequality through centralization and the need for future research on policy designs that enable centralization to yield subnational capacity that is able to remedy inequality.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.
Design, setting, and participants:
This cohort study was conducted during March 22–May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.
Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.
Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.
Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.
As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.
Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.
Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.
Commercialization of 2,4-D–tolerant crops is a major concern for sweetpotato producers because of potential 2,4-D drift that can cause severe crop injury and yield reduction. A field study was initiated in 2014 and repeated in 2015 to assess impacts of reduced rates of 2,4-D, glyphosate, or a combination of 2,4-D with glyphosate on sweetpotato. In one study, 2,4-D and glyphosate were applied alone and in combination at 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of anticipated field use rates (1.05 kg ha−1 for 2,4-D and 1.12 kg ha−1 for glyphosate) to ‘Beauregard’ sweetpotato at storage root formation (10 days after transplanting [DAP]). In a separate study, all these treatments were applied to ‘Beauregard’ sweetpotato at storage root development (30 DAP). Injury with 2,4-D alone or in combination with glyphosate was generally equal or greater than with glyphosate applied alone at equivalent herbicide rates, indicating that injury is attributable mostly to 2,4-D in the combination. There was a quadratic increase in crop injury and quadratic decrease in crop yield (with respect to most yield grades) with increased rate of 2,4-D applied alone or in combination with glyphosate applied at storage root development. However, neither the results of this relationship nor of the significance of herbicide rate were observed on crop injury or sweetpotato yield when herbicide application occurred at storage root formation, with a few exceptions. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of 2,4-D applied alone or in combination with glyphosate, although injury observed at lower rates was also a concern after initial observation by sweetpotato producers. However, in some cases, yield reduction of U.S. no.1 and marketable grades was also observed after application of 1/250×, 1/100×, or 1/10× rates of 2,4-D alone or with glyphosate when applied at storage root development.
A major concern of sweetpotato producers is the potential negative effects from herbicide drift or sprayer contamination events when dicamba is applied to nearby dicamba-resistant crops. A field study was initiated in 2014 and repeated in 2015 to assess the effects of reduced rates of N,N-Bis-(3-aminopropyl)methylamine (BAPMA) or diglycloamine (DGA) salt of dicamba, glyphosate, or a combination of these individually in separate trials with glyphosate on sweetpotato. Reduced rates of 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of the 1× use rate of each dicamba formulation at 0.56 kg ha−1, glyphosate at 1.12 kg ha−1, and a combination of the two at aforementioned rates were applied to ‘Beauregard’ sweetpotato at storage root formation (10 d after transplanting) in one trial and storage root development (30 d after transplanting) in a separate trial. Injury with each salt of dicamba (BAPMA or DGA) applied alone or with glyphosate was generally equal to or greater than glyphosate applied alone at equivalent rates, indicating that injury is most attributable to the dicamba in the combination. There was a quadratic increase in crop injury and a quadratic decrease in crop yield (with respect to most yield grades) observed with an increased herbicide rate of dicamba applied alone or in combination with glyphosate applied at storage root development. However, with a few exceptions, neither this relationship nor the significance of herbicide rate was observed on crop injury or sweetpotato yield when herbicide application occurred at the storage root formation stage. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of either salt of dicamba applied alone or in combination with glyphosate, although injury observed at lower rates would be cause for concern after initial observation by sweetpotato producers. However, in some cases yield reduction of No.1 and marketable grades was observed following 1/250×, 1/100×, or 1/10× application rates of dicamba alone or with glyphosate when applied at storage root development.
Increasing weed control costs and limited herbicide options threaten vegetable crop profitability. Traditional interrow mechanical cultivation is very effective at removing weeds between crop rows. However, weed control within the crop rows is necessary to establish the crop and prevent yield loss. Currently, many vegetable crops require hand weeding to remove weeds within the row that remain after traditional cultivation and herbicide use. Intelligent cultivators have come into commercial use to remove intrarow weeds and reduce cost of hand weeding. Intelligent cultivators currently on the market such as the Robovator, use pattern recognition to detect the crop row. These cultivators do not differentiate crops and weeds and do not work well among high weed populations. One approach to differentiate weeds is to place a machine-detectable mark or signal on the crop (i.e., the crop has the mark and the weed does not), thereby facilitating weed/crop differentiation. Lettuce and tomato plants were marked with labels and topical markers, then cultivated with an intelligent cultivator programmed to identify the markers. Results from field trials in marked tomato and lettuce found that the intelligent cultivator removed 90% more weeds from tomato and 66% more weeds from lettuce than standard cultivators without reducing yields. Accurate crop and weed differentiation described here resulted in a 45% to 48% reduction in hand-weeding time per hectare.
Field studies were conducted in 2016 and 2017 in Clinton, NC, to determine the interspecific and intraspecific interference of Palmer amaranth (Amaranthus palmeri S. Watson) or large crabgrass [Digitaria sanguinalis (L.) Scop.] in ‘Covington’ sweetpotato [Ipomoea batatas (L.) Lam.]. Amaranthus palmeri and D. sanguinalis were established 1 d after sweetpotato transplanting and maintained season-long at 0, 1, 2, 4, 8 and 0, 1, 2, 4, 16 plants m−1 of row in the presence and absence of sweetpotato, respectively. Predicted yield loss for sweetpotato was 35% to 76% for D. sanguinalis at 1 to 16 plants m−1 of row and 50% to 79% for A. palmeri at 1 to 8 plants m−1 of row. Weed dry biomass per meter of row increased linearly with increasing weed density. Individual dry biomass of A. palmeri and D. sanguinalis was not affected by weed density when grown in the presence of sweetpotato. When grown without sweetpotato, individual weed dry biomass decreased 71% and 62% from 1 to 4 plants m−1 row for A. palmeri and D. sanguinalis, respectively. Individual weed dry biomass was not affected above 4 plants m−1 row to the highest densities of 8 and 16 plants m−1 row for A. palmeri and D. sanguinalis, respectively.
Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games).We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of ‘big data’, but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
This paper summarises developments in understanding sea level change during the Quaternary in Scotland since the publication of the Quaternary of Scotland Geological Conservation Review volume in 1993. We present a review of progress in methodology, particularly in the study of sediments in isolation basins and estuaries as well as in techniques in the field and laboratory, which have together disclosed greater detail in the record of relative sea level (RSL) change than was available in 1993. However, progress in determining the record of RSL change varies in different areas. Studies of sediments and stratigraphy offshore on the continental shelf have increased greatly, but the record of RSL change there remains patchy. Studies onshore have resulted in improvements in the knowledge of rock shorelines, including the processes by which they are formed, but much remains to be understood. Studies of Late Devensian and Holocene RSLs around present coasts have improved knowledge of both the extent and age range of the evidence. The record of RSL change on the W and NW coasts has disclosed a much longer dated RSL record than was available before 1993, possibly with evidence of Meltwater Pulse 1A, while studies in estuaries on the E and SW coasts have disclosed widespread and consistent fluctuations in Holocene RSLs. Evidence for the meltwater pulse associated with the Early Holocene discharge of Lakes Agassiz–Ojibway in N America has been found on both E and W coasts. The effects of the impact of storminess, in particular in cliff-top storm deposits, have been widely identified. Further information on the Holocene Storegga Slide tsunami has enabled a better understanding of the event, but evidence for other tsunami events on Scottish coasts remains uncertain. Methodological developments have led to new reconstructions of RSL change for the last 2000 years, utilising state-of-the-art GIA models and alongside coastal biostratigraphy to determine trends to compare with modern tide gauge and documentary evidence. Developments in GIA modelling have provided valuable information on patterns of land uplift during and following deglaciation. The studies undertaken raise a number of research questions which will require addressing in future work.